Project Abstract ? Bupropion for the Prevention of Postpartum Smoking Relapse Postpartum smoking relapse rates have remained stagnant for over a decade with approximately 50% of those who are able to achieve smoking abstinence during pregnancy relapsing within the first few months after childbirth. Maternal cigarette smoking results in a significant increase in a variety of negative health consequences for both mother and child. Of women who smoke three months prior to pregnancy, 55% quit during their pregnancy. The following postpartum period presents a unique and challenging time for women to maintain smoking abstinence. Several modifiable risk factors are predictive of postpartum smoking relapse including depression, weight concerns, and smoking related symptomatology. Bupropion is uniquely suited to address each of these relapse related risk factors in postpartum women. Treatments that address these multi- faceted barriers related to postpartum smoking relapse may lead to sustained abstinence. Bupropion has proven efficacy for smoking cessation in the general population, doubling quit rates at six months. Though less explored in the literature, bupropion treatment for smoking relapse prevention has demonstrated a delay to relapse in those receiving bupropion. Yet the use of bupropion for postpartum smoking relapse prevention has not been explored. Therefore, our central hypothesis is that bupropion will prevent postpartum smoking relapse among women who quit smoking during pregnancy. To explore this hypothesis, we will conduct a two-arm, double-blind, placebo-controlled randomized clinical trial using rigorous, validated and reproducible methods that will be implemented by a team of experienced investigators who are familiar with this population. We will enroll pregnant women (n=230) who quit smoking after learning they were pregnant and are motivated to stay abstinent postpartum. Participants will be randomized to receive extended release bupropion (active 300mg or placebo once daily beginning 4 to 10 days postpartum to 12 weeks post randomization). All participants will complete the same data collection procedures (e.g., biological sample collection for hormone and cotinine analysis and completion of validated questionnaires) at baseline (gestational week 36), weekly from 4 to 10 days postpartum through 12 weeks post randomization and at weeks 12, 24, 36 and 52 post randomization. Intervention adherence will be confirmed quantitatively via high performance liquid chromatography using biological samples. The implications of this novel study, pursued by a highly skilled and productive team, will directly advance the current state of the science by expanding on the role of a known pharmacotherapy within this highly vulnerable population. Further, should our central hypothesis be supported, the dissemination of this intervention is clinically applicable, relevant and may be immediately pursued.